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Dr. Padmaja Phade

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Aqueous humour is clear colourless watery solutioncontinuously circulated from posterior chamber of theeye through out the anterior chamber

Maintenance of IOP and pathophysiology of glaucomarevolves around aq. Humour dynamics

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ANATOMY Ciliary body

Forward continuation of choroid at Ora serreta

Triangular in cut section Inner side of triangle is divided into

Pars plicata- 2-2.5mm

Pars plana- 5mm temporally, 3mm nasaly

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Microscopy

1. Supraciliary lamina- outer most condensedpart of the stroma

2. Stroma- consist of collagen tissue andfibroblast with ciliary muscle, vasculatureand nervs

3. Layer of pigmented epithelium

4. Layer of non pigmented epithelium

5. Internal limiting membrane

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Ciliary processes

70-80 Whitish finger like projections 2 X 0.5mm

Composed of central capillary network with fenestratedthin endothelium and pericytes surrounded by stromaand two layers of epithelium and ILM

Inner nonpigmented and outer pigmented epitheliumwith juxta pposed apical surfaces

Inner nonpigmented epi. Characterised by mitochondria,zonula occludentes (ZO)and lateral surfaceinterdigitations

The tight junctions contribute to the blood aqueousbarrier

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Posterior chamber

Triangular space

0.06ml of aqueous

Divided into prezonular, zonular and retrozonular space

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Anterior chamber

2.5mm deep in centre,

Contains 0.25ml aqueous

Bounded

ant-post surface of cornea,

Post- anterior surface of ciliary body and iris Comunicates through the pupil with post. Chamber

Chamber volume decreases by 0.11l/year of life

Chamber depth decreases by 0.01mm/year of life

Chamber depth is shallower in hypermtropic than myopic Chamber depth is slightly decrease during accommodation

partly by lens curvature and partly by forward translocationof lens.

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Angle of Anterior chamber Peripheral recess of ant. Chamber

Formed mainly by TM

Formed post. To ant. By1. Ciliary band

2. Scleral spur

3. Trabecular meshwork

4. Schwalbes line

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Gonioscopic grading of angle width

Grade Angle width configuration

Chances ofclosure

Structurevisible ongonioscopy

IV 35-450 Wide open Nil Schwalbes line

to ciliary bodyIII 20-350 Open Nil Schwalbes line

to scleral spur

II 200 Moderatelynarrow

Closurepossible

Schwalbes lineto TM

I 100 Very narrow High Schwalbes lineonly

0 00 Closed closed none

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Aqueous outflow system

Consist of two pathways Trabecular / conventional outflow

Uveoscleral / unconventional outflow

Trabecular meshwork

It is sieve like structure bridging the scleral sulcus cosist of 3 parts1. Uveal meshwork-

inner most, extend from iris root and ciliary body to theschwalbes line.

The trabeculea are chord like and 2-3 layer thick.

Arrangement creates 25-75 Each trabeculae has 3 concentric layers with central

collagenous core enclosed by abasement membrane andtrabecular cells.

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2. Corneoscleral meshwork From scleral spur to lateral wall of scleral sulcus

Cosist of flat sheet of trabeculae with elliptical opening rangingfrom 5-50 become progressively smaller towards the schlemmscanal

3. Juxtacanalicular meshwork

Outermost layer connects corneoscleral meshwork toschlemms canal

Consists of 2-5 layers of loosely arranged cells embedded inECM (hyluronic acid and other GAG) lined on either side byendothelial cells

Offers main resistance to aqueous flow

Outer endothelial layer of juxta canalicular meshworkcomprises inner wall of schlemms canal

Inner endothelial layer continue with corneo scleralmeshwork

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Schlemms canal Endothelium lined oval channel present in scleral sulcus

Endothelial cells of inner wall are irregular and contain giantvacuoles

Collect or channel 25-35 Intrascleral aq. Vessels

Leaving schlemms canal at oblique angles to terminate intoepiscleral veins.

Valveless, wide at their origin and taper towards theanastomosis with venous channel.

1. Direct system-

2. Indirect system- Episcleral veins

Drain ultimately in cavernous sinus via ant. Ciliary andsup. Ophthalmic vein

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Formation of Aqueous Humour Ciliary processes are the site of aqueous formation

which is primarily derived from the plasma withincapillaries of cilliary processes.

Mechanisms involved

1. Diffusion-mol of gas/solution distribute themselvesuniformly throughout the space in which they arecontained by net flux of particles from area of higherconc. to area of lower conc.

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continuation

Ficks law of diffusionRate of movt.=k( c1-c2)

K is constant which depends on nature andpermeability of memb, nature solute and solvent andtemp.

C1- conc of substance on side with higher conc.C2-conc of substance on side with lower conc.

2. Ultrafiltration- depends on hydrostatic pressure andsolute conc of plasma in capillaries of cilliaryprocesses

3. Secretion-active process against conc gradient watersol substances of large mol size and greater charge areactively secreted

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STEPS OF AQUEOUS FORMATION

Secretion basically depends on transfer of solute fromstromal surface to post chamber

This establishes an osmotic gradient driving waterpassively into aqueous .

Composition of aqueous is similar to that of proteinfree plasma except for higher ascorbic acid and

bicarbonate content.

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Continuation

1. Formation of stromal pool:

formed by ultra filtration of plasma in capillaries ofciliary processes

due to fenestrations in endothelium proteins are alsopresent in the stromal pool

this ultrafiltrate accumulates behind the tight

junctions of the NPE.

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Conti.2. Uptake of fluid from stromal pool

PE takes up solute(NaCl) by 2 major electroneutralprocesses

Na+ / H+ counter exchanger NHE1 antiport inparallel with the AE2 antiport anion counter exchanger

causing Cl- influx and HCO3- eflux carbonic

anhydrase II stimulates NaCl uptake byincreasing the delivery of H+ and HCO3- to the2 antiports.

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Conti.. Na +-K+ 2Cl- SYMPORT situated on basolateral

membrane of of PE cells rate of transport of the 3 ionsdepends on their conc gradient especially on ratio of

extracellular to intracellular Cl- net solute transferthrough symport is zero at intracellular Cl- conc of50mM

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Conti PASSIVE DIFFUSION

mostly water diffuses along osmotic gradient establishedby Nacl transport.

cell memb have low content of sphyngomyelin andcholesterol hence relative high water permeability

POTENTIAL SOLUTE RECYCLING

In order to minimize fluctuations in the cell vol due tomismatch in rates of uptake of solutes and water by PEat stromal surf and their release at aqueous surf there isautocrine regulation of these processes at the PE level

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Conti

Excess fluid and solute uptake at stromal surf thanrelease at the aqeous surf of PE , NPE

Cellular swelling

ATP release by PE and NPE

cAMP formation

Activation of Cl- channels on stromal surf

Efflux of excess Cl- and water from PE, NPE

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CONTI

3. FLUID TRANSFER THROUGH GAP JUNCTIONS

Gap junctions between PE and NPE formed byconnexins Cx43 and Cx40

Gap junctions are also present within PE and NPE butare functionally less significant

Aqueous is thus formed by parallel couplets of PE NPEcell gap junctions.

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Conti

4. FLUID TRANSFER INTO AQUEOUS HUMOUR final step in aqueous secretion.

Solutes and water are transported across the basolateral membrane ofNPE. Na+, K+ ATPase releases(70%) Na+ against electrochemical gradient

into aqueous, remaining (30%/) transported passively or by ultrafiltration.

Cl- is released along its electrochemical gradient through Cl- channels.

Water released along osmotic gradient established by solute transferinto aqueous through AQP1 and AQP4.

Bicarbonate exits through HCO3-/Cl- exchangers as well as Cl- channels.

K+ transported by secretion and diffusionAscorbic acid secreted against a conc gradient

Amino acids are secreted by 3 diff carrier proteins each for acidic , basicand neutral molecules.

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RATE OF AQUEOUS HUMOUR FORMATION 2.5micro liters/min in an undisturbed human eye

Rate of aqueous inflow is 2 times higher during wakingthan in nocturnal hours

REGULATION OF AQUEOUS FORMATION

1.Adrenergic receptors- 2 receptor stimulation lowers aqueous secretion via adeylate

cyclase inhibition. epinephrine stimulates PGF2production which lowers IOP.

2 receptor stimulation leads to increased aqueous secretionvia activation of adenylate cyclase.

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Conti..

Catecholamines

Stimulation of adenylate cyclase

Icreased c-AMP formation

activation of PKspecific protien phosphorylation

increased permeability of PE,NPE cells to solutes and

water.

increased aqueous formation

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Conti..2. Ultrafiltration and diffusion

these passive mechanisms depend on blood pressure incilliary capillaries , plasma oncotic pressure,and IOP.

3. Vasopressin

vasopressin stimulates NaCl transport through PE ,NPEand thus aqueous formation.

vasopressin levels in turn are indirectly proportional toplasma osmolarity.

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MEASUREMENT OF RATE OF AQUEOUS PRODUCTIONClass 1 methods

measure rate of appearance and dissapearance of asubstance from aqueous

1. Fluorescein techniques2. Radioactive labeled isotopes

3. Intravenous PAH technique

Class 2 methods

flow= C(Po-Pv)C= facility of aqueous outflow

Po= IOP

Pv=episcleral venous pressure

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Conti.1. Perfusion of eyes at a constant pressure

2. Tonography

3. Perilimbal suction cup method

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BIOCHEMICAL COMPOSITION OF AQUEOUS HUMOUR

Water: constitutes about 99.9% of aqueousProteins: is about 5-16 mg/dl ie1/500 of plasma protein content

(6-7g/dl)A:G ratio is same as that of plasmaIgG and IgM arepresent

plasminogen and its proactivators are presentFGF,TGF,IGF1

Amino acids:- conc varies with aqueous/plasma conc (0.08-3.14)Non colloidal constituents:- similar to that of plasma

ascorbate, lactate, pyruvate is higher than that in plasmaconc of glucose and urea is higher than that of plasmabicarbonate, ascorbate levels in post chamber is higher than in

ant chamberchloride conc in post chamber is lower than in ant chamber

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BLOOD OCULAR BARRIER BLOOD AQUEOUS BARRIER : formed by tight junctions (zonula

occludens and zonula adherans) between cells of inner NPE of ciliaryprocesses and non fenestrated epithelium of iris capillaries.

BLOOD RETINAL BARRIER :

INNER : tight junctions of retinal capillaries and endothelial cells OUTER: tight junctions between adjacent RPE Blood ocular barrier prevents proteins and large mol wt substances

from entering the ocular cavities Lipid solubility facilitates ocular penetration Medium mol wt substances penetrate at a slower rate than their transit

through capillary walls.With breakdown of blood aqueous barrier protein and antibody conc

of aqueous equilibrates with that of plasma to form SECONDARY ORPLASMOID AQUEOUS. Fibrinogen may cause clotting .

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CAUSES OF INTERRUPTION OF BLOOD OCULAR BARRIER OCULAR TRAUMA

1. mechanical : paracentesis

corneal abrasion

intraocular surgeriesstroking iris

2. Physical: X rays

atomic radiation

3. Chemical : alkaliirritants

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PATHOPHYSIOLOGICAL

1. inflamations

2. intraocular and corneal infections

3.anterior segment ischemia

PHARMACOLOGICAL1.MSH

2.Cholinergic drugs

3. Cholinesterase inhibitors4. Nitrogen mustard

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FUNCTIONS OF AQUEOUS HUMOUR

Maintenance of IOP

Metabolism of avascular stuctures of eye

Optical function Clearing function

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PHYSIOCHEMICAL PROPERTIES OF AQUEOUS

VOLUME: 0.31 ml ( 0.25ml in AC ; 0.06 ml inpost chamber)

Refractive index : 1.336 pH : 7.2 ( acidic)

Density: slightly denser than water ( 1.040: 1.025)

Osmotic pressure: hyperosmotic to plasma by 3 to5 m osmo/l

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AQUEOUS HUMOUR DYNAMICS Includes aqueous formation and drainage

Aqueous flows from post to ant chamber throughpupil and in AC flows along conventional current setup due to temp difference in ant part and post part ofAC.

From AC aqueous is drained by

1. Trabecular(conventional) outflow2. Uveoscleral( unconventional) outflow

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Ciliary process

Aq. In post. Chamber

Anterior chamber

Trabecular meshwork ciliary body

Schlemms canal suprachoroidal spaceCollector channel venous circn. Cil. Body,

sclera and orbit

Episcleral veins

Trabecular outflow90%

Uveoscleral outflow10%

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TRABECULAR OUTFLOW Drains 75 to 90% aqueous Free flow occurs through TM till the juxtacanalicular tissue

which offer some resistance to the outflow.

SPECIAL CHARACTERISTICS OF TM CELLS:I. High levels of cytoskeletal actin and lower levels of

microtubulesII. Presence of cellular vimentin and desminIII. AQP1 PROTIENSIV.

High levels of surface tPAV. GAG degrading enzymes and acid phosphatasesVI. 2 adrenergic receptors and TIGRVII. Specialized endocytic / phagocytic properties

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MECHANISM OF AQUEOUS TRANSPORT THROUGH TM

1. VACUOLATION THEORY:- vesicles and vacuoles in endothelium open

and close intermittently to transport aqueous from TM cells to

Schlemmscanal

NonVacuolated

state

Early stage ofbasal infolding

Macrovacuoleformation

Vacuolartransecellular

channelformation

Oclusion ofbasal

infolding

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Conti2. LEAKY ENDOTHELIAL CELLS

3. SONDERMANS CHANNELS : microtubules in TM cellshelp aqueous flow from corneoscleral trabecular

meshwork into lumen ofSchlemms canal .

4. CONTRACTILE MICROFILAMENTS :

5. PORES IN ENDOTHELIAL CELLS : (3m ) about 20,000

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UVEOSCLERAL OUTFLOW Drains 0.3l/min

Drains 10 to 25% of aqueous

Independent of IOP PG increase uveoscleral flow to lower the IOP

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FACILITY OF AQUEOUS OUTFLOW

Pressure gradient of 10mm of Hg between IOP andepiscleral venous plexus helps in drainage

C- value expressed as aq. Outflow in l/min/mm of Hg

It represents quantitative aproximation of state of aq.Drainage system

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Measurements of C value1. Perfusion method

C= flow rate / Pi Po

Independent of ocular rigidity and corneal curvature

C=0.28 l/min/mm of Hg

2. Tonography

Most commonly used non invasive method

3. Suction cup method

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97.5% population has C value >0.18

Most glaucoma pt. has C value

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